茵陈蒿汤对重症急性胰腺炎大鼠相关急性肝损伤的作用及p62-keap1-Nrf2信号通路的影响

Effects of Yinchenhao Decoction on Severe Acute Pancreatitis-related Acute Liver Injury and p62-keap1-Nrf2 Signaling Pathway in Rats

目的观察茵陈蒿汤对重症急性胰腺炎(SAP)大鼠相关急性肝损伤的作用及p62-keap1-Nrf2信号通路的影响。方法将雄性8周龄SD大鼠30只均分为3组:假手术组、模型组和茵陈蒿汤组。模型组与茵陈蒿汤组用逆行胰胆管注射5%牛磺胆酸钠建立SAP模型,以0.2 m L/min的均匀速度注射到胆管内。假手术组注射等量生理盐水。造模2 h后茵陈蒿汤组以5 g/kg进行灌胃,对照组和模型组给予等量生理盐水。24 h后处死大鼠后进行相关检测。结果假手术组未见病理损害,模型组和茵陈蒿汤组出现不同程度的小叶中心肝细胞坏死,肝细胞颗粒变性,炎性细胞浸润,但茵陈蒿汤组的病理损伤较模型组明显减轻。与假手术组比较,模型组和茵陈蒿汤组大鼠肝脏系数均增高、血清中血清淀粉酶(AMY)、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(GOT)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)含量均增高,肝组织中p62、keap1和Nrf2蛋白表达均增高;与模型组比较,茵陈蒿汤组大鼠肝脏系数降低,血清中AMY、ALT、GOT、TNF-α和IL-1β含量均降低,肝组织中p62、keap1和Nrf2蛋白表达均降低。结论茵陈蒿汤能通过抑制p62-keap1-Nrf2信号通路从而减轻SAP大鼠急性肝损伤。

Objective:To investigate effects of Yinchenhao Decoction on severe acute pancreatitis-related acute liver injury and p62-keap1-Nrf2 signaling pathway in rats.Methods:30 male 8-week-old SD rats were divided into three groups:sham-operated group,the model group and Yinchenhao Decoction group.Rats were made into SAP models and received the corresponding treatments.24 h later,rats were executed for the detection of the related factors.Results:There was no pathological damage in sham-operated group.In the model group and Yinchenhao Decoction group,hepatocyte necrosis,hepatocyte granular degeneration and inflammatory cell infiltration were observed in different degrees.However,the pathological damage in Yinchenhao Decoction group was significantly less than that in the model group.Compared with sham-operated group,the liver coefficient,serum AMY,ALT,GOT,TNF-αand IL-1βcontents,and the expression of p62,keap 1 and Nrf2 protein in liver tissue were increased in the model group and Yinchenhao Decoction group.Compared with the model group,the above indices of Yinchenhao Decoction group were lower.Conclusion:Yinchenhao Decoction can alleviate acute liver injury in SAP rats by inhibiting p62-keap1-Nrf2 signaling pathway.